P2–378: Motor dysfunction in the 12‐month‐old 5xFAD mouse model of Alzheimer's disease
Bibliographic record
Abstract
The 5xFAD mouse model of Alzheimer's Disease (AD) may be a useful model of the motor impairments which can develop in AD because they develop age-related motor dysfunction at 9 months of age (Jawhar et al., 2012, Neurobiol. Aging,33, 196.e29–40). We therefore conducted a comprehensive analysis of the motor phenotype of 5xFAD mice, and examined deficits in the generation of motor output at the neuro-muscular junction as a possible cause of these motor deficits. The motor abilities of female 5xFAD mice and wild-type controls (C57BL/6J x SJL/J F1) were compared at 11–13 months of age. Mice completed a comprehensive test battery which assessed locomotor activity (open-field), gait (paw-print analysis), motor coordination and learning (rota-rod), balance (balance-beam) and motor strength/coordination (grid- and string-suspension tests). Electrophysiological force measurements were also completed with the soleus muscle of the hind leg, to determine if differences were present in the generation of motor output following direct stimulation of the soleus nerve. The 5xFAD mice showed decreased body weight relative to wild-type mice, along with decreased locomotor activity on the open-field, abnormal gait, impaired motor coordination and learning on the rota-rod, and impaired balance. Impairments in the string- and grid-suspension tests likely reflect impairment in motor coordination rather than motor strength, as no differences were found in twitch or tetanus force measurements with the soleus muscle. This study demonstrates that impairments are present in locomotor activity, gait, motor coordination and balance in the 5xFAD mouse. These deficits are likely due to impaired function of pyramidal and/or extra-pyramidal motor systems of the brain and spinal cord, as the generation of motor output remains unimpaired following stimulation of lower motor neurons. These motor disabilities must be considered when using 5xFAD mice in tests of cognitive function which rely on normal motor ability (i.e. Morris water maze). We continue to investigate the neural and genetic causes of these motor dysfunctions.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.010 | 0.005 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".